Chronic kidney disease

Nature Reviews Disease Primers, Год журнала: 2017, Номер 3(1)

Опубликована: Ноя. 22, 2017

Язык: Английский

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Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis

Nature Reviews Nephrology, Год журнала: 2016, Номер 12(8), С. 453 - 471

Опубликована: Июнь 6, 2016

Язык: Английский

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Podocyte injury and its consequences

Kidney International, Год журнала: 2016, Номер 89(6), С. 1221 - 1230

Опубликована: Март 19, 2016

Podocytes maintain the glomerular filtration barrier, and stability of this barrier depends on their highly differentiated postmitotic phenotype, which also defines particular vulnerability glomerulus. Recent podocyte biology gene disruption studies in vivo indicate a causal relationship between abnormalities single molecules proteinuria glomerulosclerosis. live under various stresses pathological stimuli. They adapt to homeostasis, but excessive stress leads maladaptation with complex biological changes including loss integrity dysregulation cellular metabolism. Podocyte injury causes detachment from basement membrane. In addition "sick" podocytes detachment, our understanding responses following needs address pathways sclerosis. Studies have found variety dysfunction vivo, such as podocyte-endothelial cross talk activation podocyte-parietal cell interactions, all help us understand scenario its consequences. This review focuses aspects adaptive or maladaptive that lead major consequence,

Язык: Английский

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Focal Segmental Glomerulosclerosis

Clinical Journal of the American Society of Nephrology, Год журнала: 2017, Номер 12(3), С. 502 - 517

Опубликована: Фев. 27, 2017

Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology primary FSGS plasma factor with responsiveness to immunosuppressive therapy and risk recurrence after transplant-important characteristics. In contrast, adaptive associated excessive nephron workload due increased body size, reduced capacity, or single glomerular hyperfiltration certain diseases. Additional etiologies are now recognized as drivers FSGS: high-penetrance genetic mutations in one nearly 40 genes, virus-associated FSGS, medication-associated FSGS. Emerging data support the identification sixth category: APOL1 allele-associated individuals sub-Saharan ancestry. classification particular patient relies on integration findings from clinical history, laboratory testing, biopsy, some patients, testing. biopsy can be helpful, clues provided by features light microscopy (

Язык: Английский

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Cellular and molecular mechanisms of kidney fibrosis

Molecular Aspects of Medicine, Год журнала: 2018, Номер 65, С. 16 - 36

Опубликована: Июнь 22, 2018

Язык: Английский

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Arachidonic Acid Metabolism and Kidney Inflammation

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(15), С. 3683 - 3683

Опубликована: Июль 27, 2019

As a major component of cell membrane lipids, Arachidonic acid (AA), being the lipid content, is mainly metabolized by three kinds enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Based on these metabolic pathways, AA could be converted into various metabolites that trigger different inflammatory responses. In kidney, prostaglandins (PG), thromboxane (Tx), leukotrienes (LTs) hydroxyeicosatetraenoic acids (HETEs) are generated from AA. An increased level (PGs), TxA2 leukotriene B4 (LTB4) results in damage to kidney. Moreover, LTB4-leukotriene receptor 1 (BLT1) axis participates acute kidney injury via mediating recruitment renal neutrophils. addition, can regulate ion transport through 19-hydroxystilbenetetraenoic (19-HETE) 20-HETE, both which produced monooxygenase. Epoxyeicosatrienoic (EETs) CYP450 enzyme also plays paramount role during inflammation process. For example, 14 15-EET mitigated ischemia/reperfusion-caused tubular epithelial damage. Many drug candidates target metabolism pathways developed treat inflammation. These observations support an extraordinary interest wide range studies interventions aiming control

Язык: Английский

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The cell biology of renal filtration

The Journal of Cell Biology, Год журнала: 2015, Номер 209(2), С. 199 - 210

Опубликована: Апрель 27, 2015

The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate functionally elegant structure called renal glomerulus. Normal glomerular retains circulating cells valuable macromolecular components plasma blood, resulting urine with just trace amounts proteins. Endothelial capillaries, podocytes wrapped around them, fused extracellular matrix these form altogether comprise filtration barrier, a dynamic highly selective filter that sieves on basis molecular size electrical charge. Current understanding structural organization cellular draws from studies human diseases animal models dysfunction.

Язык: Английский

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Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

Journal of the American Society of Nephrology, Год журнала: 2018, Номер 29(3), С. 759 - 774

Опубликована: Янв. 10, 2018

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury depletion. Subclasses of include primary, genetic, secondary forms, the latter comprising maladaptive, viral, drug-induced FSGS. Despite sharing certain clinical features, these subclasses differ noticeably in management prognosis. Without an accepted nongenetic biomarker discriminates among types, classification patients is often challenging. This review summarizes including onset severity proteinuria as well presence nephrotic syndrome, may aid identifying specific subtype. The characterized segmental sclerosis must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features pathognomonic for particular subcategory. characteristics foot process effacement on electron microscopy, while helpful discriminating between primary maladaptive FSGS, little utility detecting genetic forms When cannot classified clinicopathologic assessment, analysis should offered. Next generation DNA sequencing enables cost-effective screening multiple genes simultaneously, but determining pathogenicity detected variant A more systematic evaluation patients, suggested herein, will likely improve therapeutic outcomes design future trials

Язык: Английский

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Molecular pathways that drive diabetic kidney disease

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(4)

Опубликована: Фев. 14, 2023

Kidney disease is a major driver of mortality among patients with diabetes and diabetic kidney (DKD) responsible for close to half all chronic cases. DKD usually develops in genetically susceptible individual as result poor metabolic (glycemic) control. Molecular genetic studies indicate the key role podocytes endothelial cells driving albuminuria early diabetes. Proximal tubule changes show strong association glomerular filtration rate. Hyperglycemia represents cellular stress by altering metabolism imposing an excess workload requiring energy oxygen proximal cells. Changes induce adaptive hypertrophy reorganization actin cytoskeleton. Later, mitochondrial defects contribute increased oxidative activation inflammatory pathways, causing progressive function decline fibrosis. Blockade renin-angiotensin system or sodium-glucose cotransporter associated protection slowing decline. Newly identified molecular pathways could provide basis development much-needed novel therapeutics.

Язык: Английский

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Wnt/β-catenin signalling and podocyte dysfunction in proteinuric kidney disease

Nature Reviews Nephrology, Год журнала: 2015, Номер 11(9), С. 535 - 545

Опубликована: Июнь 9, 2015

Язык: Английский

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